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Tetrahedron 70 (2014) 270e275

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Tetrahedron

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Eco-friendly synthesis of guanidinyltetrazole compounds and5-substituted 1H-tetrazoles in water under microwave irradiation

Mahmoud Abd El Aleem Ali Ali El Remaily a,*, Shaaban K. Mohamed b,c

aChemistry Department, Faculty of Science, Sohag University, 82524 Shag, EgyptbChemistry and Environmental Division, Manchester Metropolitan University, Manchester M1 5GD, England, United KingdomcChemistry department. Faculty of Science, Minia University, 61519 El-Minia, Egypt

a r t i c l e i n f o

Article history:Received 20 October 2013Received in revised form 16 November 2013Accepted 19 November 2013Available online 23 November 2013

Keywords:Guanidinyltetrazoles5-Substituted 1H-tetrazolesMicrowave irradiationEnvironmentally benign protocol

* Corresponding author. Tel.: þ20 1143627127; faxdress: msremaily@ugr.es (M.A.E.A.A.A. El-Remaily).

0040-4020/$ e see front matter � 2013 Elsevier Ltd.http://dx.doi.org/10.1016/j.tet.2013.11.069

a b s t r a c t

We have developed simple, short time, cost effective, purification of products by non-chromatographicmethods and environmentally benign protocol for the synthesis of guanidinyltetrazoles and 5-substituted 1H-tetrazoles derivatives via [2,3]cyclo-addition reaction of nitriles and azide derivatives inwater under microwave irradiation. All the synthesized products are screened for their in vitro anti-microbial activity. The synthesized compounds were obtained in excellent yield (85e98%).

� 2013 Elsevier Ltd. All rights reserved.

1. Introduction

Green chemistry techniques continue to grow in importance analternative processes to conserve resources and reduce costs. Thereplacement of conventional solvents with water, which is harm-less to health and is available in large quantities, is an interestingbasic approach along these lines.1e3 The application of microwaveirradiation to organic synthesis for conducting reactions at accel-erated rates is an emerging technique. In fact, in recent years, theuse of microwaves has become popular among chemists both asa means to improve classical organic reactions (shortening reactiontimes and/or improving yields) and promote new reactions.4

Availability of suitable commercial microwave equipment, do-mestic oven sand mono-mode reactors has also contributed to thedevelopment of this technique significantly.5 Tetrazoles are het-erocyclic compounds not been in nature. Such compounds havea wide range of applications in pharmaceutical chemistry6 espe-cially in drug in isosteric replacement of carboxylic acid moiety.7

Biphenyltetrazoles are used for the synthesis of sartan familydrugs8 and also as ligands in the synthesis of imidoylazides.9 Tet-razole compounds are widely used as propellants and explosives.10

In crop protection they are used as plant growth regulators,11

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herbicides, andfungicides.12 In addition to this they possess anti-biotic,13 anti-allergic,14 antagonists,15 antihypertensive,16 and anti-viral activities.17 Recently tetrazole moieties were widely usedfor binding aryl thiotetrazolylacetanilides with HIV-1 reversetranscriptase.18

On other hand; guanidines are structurally novel molecules re-ported to exhibit remarkable biological and pharmacological ac-tivities, which are affected by the guanidine functionality.19,20

Guanidine containing drugs, such as MIBG and MGBG were shownover several decades to have antitumor properties and have beensubjected to intense preclinical and clinical evaluation.21 Guanidinecompounds are also known to be useful basic catalysts.22,23 Thesynthesis of guanidine derivatives has also attracted continued re-search interests in recent years, resulting in many new efficientsynthetic methods and guanidinylation reagents for different clas-ses of guanidine compounds.24e27 In this concept, we herein reportthe synthesis and crystal structure of the title compound.

In last decade, Sharpless introduced the term ‘click chemistry’for synthesis of tetrazoles inwater requiring stoichiometric amountof Zn(II) salts.28 Based on above findings, we herein report syn-thesis of new derivatives of guanidinyltetrazole and 5-substituted1H-tetrazole derivatives via reaction of the precursors dicyandia-mide (Schemes 1 and 2) or nitriles (Scheme 3) with azide de-rivatives in water under microwave irradiation as an environmentally benign protocol. All products have been deposited in ex-cellent yields in a recognized short time.

NC NH

NH

NH2 Water

ZnBr2 or AcOH

NaN3

NN

NNHNH

NH

NH2

OH

N3

NN

NNNH

NH

NH2

OH

NH2

N3

NN

NNNH

NH

NH2

NH2

C10

N3HOOC( )

NN

NNNH

NH

NH2

C10

HOOC( )

C17

N3CH3 ( )NN

NNNH

NH

NH2

C17

CH3 ( )

N3

NN

N N

NHNH

NH2

O

OAc

AcOOAc

OAc

N3 NN

NNNH

NH

NH2

O

OAc

AcOOAc

OAc

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

Scheme 1. Synthesis of gunaylaminotetrazole derivatives 9e15.

M.A.A. El-Remaily, S.K. Mohamed / Tetrahedron 70 (2014) 270e275 271

2. Results and discussion

The reactions of dicyandiamide 1 with mono azide derivatives2e8 in water under microwave irradiation (10 mine1 h) in pres-ence of ZnBr2 or AcOH as a catalyst gave the corresponding gua-nidinyltetrazole derivatives 9e15 (Scheme 1). The reaction hasbeen rationalized as 2þ3 cycloaddition mechanism. Due to thepartial solubility of some azide derivatives in water, we used to usea mixed solvent of water and ethanol (v/v). The Lewis acid catalystsZnBr2 or AcOH have been employed individually but the resultsshowed the ZnBr2is more efficient than AcOH in some cases (seeTable 1).

In a similar manner, bis-, tris-, and tetris-terazolo guanidinecompounds 21e25 were synthesized from the reaction ofthe precursor 1 with di, tri, and tetra azide derivatives 16e20(Scheme 2).

Reaction of sodium azide alone with malononitrile, ethyl cya-noacetate, benzylidene malononitrile or ethyl (2E)-2-cyano-3-

phenylacrylate under same employed reaction conditions gave 5-substituted 1H-tetrazoles derivatives 30e33 (Scheme 3).

3. Anti-bacterial activity

All products were dissolved in DMSO. In order to ensure thatthe solvent had no effect on bacterial growth or enzymatic ac-tivity, negative controls were established using DMSO at the sameconcentrations. The inhibitory effect of synthesized compoundson the in vitro growth of a broad spectrum of bacteria repre-senting different types of Gram-positive and Gram-negative bac-teria, namely Bacillus cereus, Bacillus subtilis, Escherichia coli,and Pseudomonas aeruginosa was evaluated using agar diffusionmethod (cup and plate method).29e31 DMSO was used as a solventcontrol. All plates were incubated at 37�0.5 �C for 24 h. Thezone of inhibition of compounds was measured using a mm scale(Table 2).

NC NH

NH

NH2 Water

ZnBr2 or AcOH

N3

N3

NN

NN

NHNH

NH2

N

NN

N

NHNH

NH2

1

16

17

21

N3

N3

NNN

NN

NH

NHNH2

NN

NNH

NHNH2

N3

N3

N

N

N N

NNH

NH NH2

NN

N

NH

NHNH2

N3N3

N3

N3

N3N3

N3

N N

NNN

NN

NH NH2

NH

N

NN

NH NH2

NHN

N N

NHNH2

NH

N

N N

NHNH2

NH

22

18

23

19

20

25

24

N

N

NN

N

N

NH

NH

NH2NN

N NH NH

NH2

NN

N NH NH

NH2

Scheme 2. Synthesis of gunaylaminotetrazole derivatives 21e25.

Table 1Yield of products and reaction time when ZnBr2 and ACOH catalysts have beenemployed

No ofcomp.

Yield (%)ZnBr

Yield(%) AcOH

Time ofreaction(min)

No ofcomp.

Yield(%) ZnBr

Yield (%)AcOH

Time ofreaction(min)

9 98 94 10 22 87 85 1810 94 90 12 23 90 88 2511 95 92 12 24 90 85 3012 95 91 20 25 87 82 4513 91 88 17 30 82 80 1014 87 87 25 31 85 80 1215 90 86 60 32 80 72 1521 85 84 20 33 84 81 13

Water

ZnBr2 or AcOH

NC

CN

2

26

31

32

29

NaN3

NN

NH

NNN

NH

N

NC

COOEt27 COOEtN

N

NH

N

CN

CN

COOEt

CN

NN

NH

N

N

N

NH

N

33

COOEt

NN

NH

N

28

30

Scheme 3. Synthesis of 5-substituted 1H-tetrazoles derivatives 30e33.

M.A.A. El-Remaily, S.K. Mohamed / Tetrahedron 70 (2014) 270e275272

Most of compounds have showed good inhibitory effect againstthe employed bacteria, particularly compounds 9, 11, 14, 22, 24, 25,30, 31, and 33.

3.1. Antifungal studies

Antifungal activity was also done by disk diffusion method. Forassaying antifungal activity Penicillium purpurogenum, Aspergillusflavus, and Trichothecium rosium were inoculated in SabouraudDextrose broth medium (Hi-Media Mumbai) and incubated for48e72 h at 35 �C, and Subsequently a suspension of about

Table 2Results of anti-bacterial evaluation of synthesized compounds

Zone of inhibition in mm (MIC in mg/mL)

Antibacterial strains

No Bacillus cereus Bacillus subtilis Escherichia coli Pseudomonas aeruginosa

9 22 (40) 21 (30) 22 (30) 21 (30)10 20 (30) 20 (30) 20 (30) 20 (30)11 22 (40) 21 (30) 20 (40) 21 (40)12 20 (30) 21 (30) 19 (30) 19 (30)13 18 (40) 19 (30) 20 (30) 19 (30)14 22 (40) 22 (40) 22 (30) 22 (40)15 22 (40) 21 (30) 22 (40) 18 (40)21 20 (30) 19 (30) 19 (30) 18 (30)22 21 (40) 21 (30) 21 (30) 21 (30)23 19 (30) 19 (30) 19 (30) 20 (30)24 22 (40) 21 (30) 22 (30) 21 (30)25 22 (40) 21 (30) 20 (40) 21 (40)30 22 (30) 22 (30) 22 (30) 22 (30)31 22 (30) 22 (30) 20 (30) 21 (30)32 20 (40) 19 (40) 20 (30) 20 (40)33 20 (30) 22 (40) 20 (30) 20 (30)

M.A.A. El-Remaily, S.K. Mohamed / Tetrahedron 70 (2014) 270e275 273

1.6�104e6�104 c.f.u./mL was introduced on to the surface of sterileagar plates, and a sterile glass spreader was used for even distri-bution of the inoculums. The discs measuring 6 mm in diameterwere prepared from Whatman No. 1 filter paper and sterilized bydry heat at 140 �C for 1 h. The sterile discs previously soaked ina known concentration of the test compounds were placed inSabouraud Dextrose Agar (SDA) plates.

Solvent and growth controls were kept. Fluconazole (30 mg/mL)was used as positive control. While the disk poured in DMSO wasused as negative control. The plates were inverted and incubatedfor 48e72 h at 35 �C. The susceptibility was assessed on the basis ofdiameter of zone of inhibition against albicans and non-albicansstrains of fungi. The investigation of antifungal screening datarevealed that all the tested compounds showed moderate to goodfungal inhibition. Inhibition zones were measured and comparedwith the controls. The fungal zones of inhibition values are given inTable 3.

Table 3Results of antifungal activity

Zone of inhibition in mm (MIC in mg/mL)

Antifungal strains

No Penicillium purpurogenum Aspergillus flavus Trichothecium rosium

9 17 (40) 20 (30) 18 (30)10 19 (30) 19 (30) 21 (30)11 22 (30) 22 (30) 20 (30)12 20 (30) 20 (30) 19 (30)13 20 (30) 19 (30) 20 (30)14 20 (40) 20 (40) 22 (40)15 20 (30) 20 (30) 20 (40)21 19 (30) 21 (30) 19 (30)22 22 (40) 19 (30) 21 (30)23 18 (30) 20 (30) 19 (40)24 21 (40) 22 (40) 21 (30)25 22 (40) 21 (30) 22 (40)30 21 (30) 22 (30) 20 (40)31 20 (40) 22 (40) 20 (30)32 19 (30) 19 (40) 19 (30)33 20 (40) 19 (30) 20 (30)

The results showed that compounds 11, 24, 25, and 30 possessthe highest antifungal growth while compound 9 showed thelowest effect.

The MIC of all synthesized compounds was determined bya micro dilution method. The respective clinical strain was spreadseparately on the medium. The wells were created using a stainlesssteel sterilized cork borer under aseptic conditions. The synthe-sized compounds at different concentrations viz. 10, 20, 30, 40, and50 mg was dissolved in DMSO and later loaded into correspondingwells. The results are recorded in Tables 2and 3.

Looking at results in Tables 2and 3, it is worthy to mention thatcompounds 14 and 30 have showed the best inhibitors for bacterialand compound 25 is the highest inhibitor for fungal growth. Thisactivity might be attributed to the symmetrical tetrazoles structureat 25 and 30 and due to existence of adamantly moiety for com-pound 14.

4. Experimental

4.1. General

All melting points are uncorrected and were recorded on Melt-Temp II melting point apparatus. IR spectra were measured as KBrpellets on a Shimadzu DR-8001 spectrometer. 1H NMR spectrawererecorded on a Varian Gemini at 300 MHz using TMS as an internalreference and DMSO-d6 as a solvent. Mass spectra were performedon a Shimadzu GCeMS-QP 1000 mass spectrometer at 70 eV. Allcompounds were checked for their purity on TLC plates.

4.2. General procedure for synthesis of gunanidinyltetrazoles9e15 and 21e25

In a 50 mL round bottom flask dicyandiamide 1 (1 mmol) andazide derivatives 2e8 and 16e20 (1 mmol) were taken in presenceof ZnBr2 or glacial AcOH in water (15 mL). Then the reaction mix-ture was irradiated with microwave for 10 mine1 h (see Table 1).The reaction progress was monitored by TLC till completion. Theresulting solid product was filtered off and washed with water. Allproducts were pure enough for IR and NMR spectroscopic analyses.However, the products were further purified by recrystallizationfrom ethanol.

4.2.1. 1-(2H-Tetrazol-5-yl)guanidine 9. Yield 98%, Mp >320 �C. FTIR(KBr, cm�1): 3376, 3254, 3180; 1H NMR (300 MHz, DMSO-d6):d 11.10 (s, 1H), 7.61 (s, 4H); 13C NMR (300 MHz, DMSO-d6): d 162.9,159.8; ESI MS (m/z): 127.108 (Mþ).

4.2.2. 1-[2-(2-Hydroxyethyl)-2H-tetrazol-5-yl]guanidine 10. Yield94%, Mp 282e284 �C. FTIR (KBr, cm�1): 3425, 3381, 3278, 3102,2875; 1H NMR (300 MHz, DMSO-d6): d 11.78 (s, 1H), 7.64 (s, 4H),4.54 (t, 2H), 4.46 (t, 2H); 13C NMR (300 MHz, DMSO-d6): d 163.2,159.7, 57.4, 48.6; ESI MS (m/z): 171.16 (Mþ).

4.2.3. 1-[2-(2-Aminoethyl)-2H-tetrazol-5-yl]guanidine 11. Yield95%, Mp 260e262 �C. FTIR (KBr, cm�1): 3452, 3385, 3275, 3123,2895; 1H NMR (300MHz, DMSO-d6): d 7.62 (s, 4H), 4.49 (t, 2H), 4.31(s, 2H), 3.92 (t, 2H); 13C NMR (300 MHz, DMSO-d6): d 163.1, 159.8,51.3, 38.7; ESI MS (m/z): 170.18 (Mþ).

4.2.4. 11-(5-Carbamimidamido-2H-tetrazol-2-yl)undecanoic acid12. Yield 95%, Mp >320 �C. FTIR (KBr, cm�1): 3402, 3388, 3278,3117, 2879, 1705; 1H NMR (300MHz, DMSO-d6): d 11.80 (s, 1H), 7.60(s, 4H), 4.50 (t, 2H), 2.37 (t, 2H), 2.19e1.22 (m, 16H); 13C NMR(300 MHz, DMSO-d6): d 181.5, 162.9, 159.8, 53.5, 37.2, 29.8, 29.7,29.6, 29.5, 29.4, 24.9, 24.1; ESI MS (m/z): 311.38 (Mþ).

4.2.5. Imino(2-octadecyl-2H-1,2,3,4-tetraazol-5-ylamino)methyl-amine 13. Yield 91%, Mp >320 �C. FTIR (KBr, cm�1): 3380, 3284,3164, 3044; 1H NMR (300 MHz, DMSO-d6): d 7.61 (s, 4H), 4.79 (t,

M.A.A. El-Remaily, S.K. Mohamed / Tetrahedron 70 (2014) 270e275274

2H), 2.24e1.32 (m, 30H), 1.20 (9, 2H), 0.91 (t, 3H); 13C NMR(300 MHz, DMSO-d6): d 162.8, 159.7, 53.5, 32.1, 29.8e29.3 (10C),27.1, 24.9, 19.8, 13.1; ESI MS (m/z): 379.58 (Mþ).

4.2.6. 1-(2-Adamantan-1-yl-2H-tetrazol-5-yl)guanidine 14. Yield87%, Mp 242e245 �C. FTIR (KBr, cm�1): 3395, 3284, 3160, 2895; 1HNMR (300 MHz, DMSO-d6): d 6.89 (s, 4H), 3.05 (m, 6H), 2.07 (m,3H), 1.64 (m, 6H); 13C NMR (300 MHz, DMSO-d6): d 163.1, 159.8,61.3, 38.6, 37.4, 26.1; ESI MS (m/z): 261.32 (Mþ).

4.2.7. 2-[5-Amino(imino)methylamino-2H-1,2,3,4-tetraazol-2-yl]-3,5-di(methylcarbony-loxy)-6-methylcarbonyloxymethyltetrahydro-2H-4-pyranyl acetate 2-(4-bromo-phenyl)-4,5-diphenyl-1H-imidaz-ole 15. Yield 90%, Mp 294e296 �C. FTIR (KBr, cm�1): 3387, 3275,3115, 1724; 1H NMR (300 MHz, DMSO-d6): d 7.1 (d, 1H), 6.89 (s, 4H),6.04 (t,1H), 5.34 (t, 1H), 5.14 (t, 1H), 4.32 (d, 2H), 4.11 (m,1H), 2.11 (s,3H), 2.00 (s, 3H), 1.96 (s, 6H); 13C (300 MHz, DMSO-d6): d 171.1,169.9, 168.2, 163.1, 159.7, 93.2, 67.9, 66.2, 66.0, 64.4, 61.8, 20.7, 20.5,20.3; ESI MS (m/z): 461.43 (Mþ).

4.2.8. N5-Amino(imino)methyl-2-2-[5-amino(imino)methylamino-2H-1,2,3,4-tetraazol-2-yl]ethyl-2H-1,2,3,4-tetraazol-5-amine21. Yield 85%, Mp 300e302 �C. FTIR (KBr, cm�1): 3387, 3261, 3114;1H NMR (300 MHz, DMSO-d6): d 6.69 (s, 8H, 4NHþ2NH2), 5.61 (s,4H, 2CH2); 13C NMR (300 MHz, DMSO-d6): d 163.2, 159.7, 48.3; ESIMS (m/z): 280.25 (Mþ).

4.2.9. N5-Amino(imino)methyl-2-2-[5-amino(imino)methylamino-2H-1,2,3,4-tetraazol-2-ylmethyl]benzyl-2H-1,2,3,4-tetraazol-5-amine22. Yield 87%, Mp >320 �C. FTIR (KBr, cm�1): 3882, 3276, 3160; 1HNMR (300 MHz, CDCl3): d 7.81e7.15 (m, 4H), 6.65 (s, 8H,4NHþ2NH2), 5.53 (s, 4H, 2CH2); 13C NMR (300 MHz, CDCl3):d 162.9, 159.8, 141.1, 133.9, 132.6, 55.5; ESI MS (m/z): 356.35 (Mþ).

4.2.10. N5-Amino(imino)methyl-2-3-[5-amino(imino)methylamino-2H-1,2,3,4-tetraazol-2-ylmethyl]benzyl-2H-1,2,3,4-tetraazol-5-amine23. Yield 90%, Mp >320 �C. FTIR (KBr, cm�1): 3889, 3284, 3124; 1HNMR (300 MHz, CDCl3): d 8.19 (s, 1H), 7.80e7.22 (m, 3H), 6.76(s, 8H, 4NHþ2NH2), 5.38 (s, 4H, 2CH2); 13C NMR (300 MHz, CDCl3):d 163.4, 158.8, 148.3, 134.1, 132.2, 131.8, 58.9; ESI MS (m/z):356.35 (Mþ).

4.2.11. N5-Amino(imino)methyl-2-3,5-di[5-amino(imino)methyl-amino-2H-1,2,3,4-tetraazol-2-ylmethyl]-2,4,6-trimethylbenzyl-2H-1,2,3,4-tetraazol-5-amine 24. Yield 90%, Mp >320 �C. FTIR (KBr,cm�1): 3887, 3272, 3132; 1H NMR (300 MHz, CDCl3): d 6.81 (s, 12H,6NHþ3NH2), 5.25 (s, 6H, 3CH2), 2.10 (s, 9H, 3CH3); 13C NMR(300 MHz, CDCl3): d 163.1, 159.2, 132.9, 124.7, 51.8, 18.2; ESI MS (m/z): 537.55 (Mþ).

4.2.12. N5-Amino(imino)methyl-2-2,4,5-tri[5-amino(imino)methyl-amino-2H-1,2,3,4-tetraazol-2-ylmethyl]benzyl-2H-1,2,3,4-tetraazol-5-amine 25. Yield 87%, Mp 290e292 �C. FTIR (KBr, cm�1): 3880,3266, 3242; 1H NMR (300 MHz, CDCl3): d 8.87 (s, 2H, 2CH arom),6.65 (s, 16H, 8NHþ4NH2), 5.53 (s, 8H, 4CH2); 13C NMR (300 MHz,CDCl3): d 163.1, 158.4, 144.2, 136.6, 55.8; ESI MS (m/z): 634.59 (Mþ).

4.3. General procedure for 5-substituted 1H-tetrazoles 30e33

A mixture of sodium azide (6 mmol) and malononitrile(2 mmol), ethyl cyanoacetate (1 mmol), benzylidene malononitrileor ethyl (2E)-2-cyano-3-phenylacrylate (1 mmol) was taken inpresence of ZnBr2 or glacial AcOH in water (15 mL). The reactionmixture was irradiated by microwave and monitored by TLC tillcompletion after 10 mine25 min (see Table 1). The product was

precipitated on hot, filtered off, washed with water, and recrystal-lized from ethanol.

4.3.1. 5-(2H-1,2,3,4-Tetraazol-5-ylmethyl)-2H-1,2,3,4-tetraazole30. Yield 82%, Mp >320 �C. FTIR (KBr, cm�1): 3384, 3275, 3118; 1HNMR (300 MHz, DMSO-d6): d 8.56 (s, 2H, 2NH), 3.89 (s, 2H, CH2);13C NMR (300 MHz, DMSO-d6): d 153.2, 22.4; ESI MS (m/z): 152.12(Mþ).

4.3.2. Ethyl 2-(2H-1,2,3,4-tetraazol-5-yl)acetate 31. Yield 85%, Mp>320 �C. FTIR (KBr, cm�1): 3388, 3271, 3114, 1726; 1H NMR(300 MHz, DMSO-d6): d 8.54 (s, 1H, NH), 4.05 (q, 2H, CH2), 3.47 (s,2H, CH2), 1.22 (t, 3H, CH3); 13C NMR (300 MHz, DMSO-d6): d 164.2,151.1, 60.2, 38.7, 14.1; ESI MS (m/z): 156.14 (Mþ).

4.3.3. 2-Phenyl-1,1-di(2H-1,2,3,4-tetraazol-5-yl)ethylene 32. Yield80%, Mp>320 �C. FTIR (KBr, cm�1): 3388, 3273, 3121, 1611; 1H NMR(300 MHz, DMSO-d6): d 8.67 (s, 2H, 2NH), 7.81e7.42 (m, 5H, arom),7.12 (s,1H, CH); 13C NMR (300MHz, DMSO-d6): d 154.4,150.8,138.6,132.3, 131.5, 128.8, 117.2; ESI MS (m/z): 240.23 (Mþ).

4.3.4. Ethyl (E)-3-phenyl-2-(2H-1,2,3,4-tetraazol-5-yl)-2-propenoate33. Yield 84%, Mp >320 �C. FTIR (KBr, cm�1): 3387, 3270, 3129,1727, 1611; 1H NMR (300 MHz, DMSO-d6): d 8.63 (s, 1H, NH),7.80e7.42 (m, 5H, arom), 7.18 (s, 1H, CH), 4.10 (q, 2H, CH2), 1.25 (t,3H, CH3); 13C NMR (300 MHz, DMSO-d6): d 162.1, 152.9,150.1, 138.2, 132.0, 131.1, 128.5, 117.0, 61.6, 13.9; ESI MS (m/z):244.25 (Mþ).

Acknowledgements

The authors are deeply gratitude Granada University in Spain,Sohag University in Egypt and Manchester Metropolitan Universityin England for supporting and facilitating this study.

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